Out-of-hospital cardiac arrest in children in Norway: A national cohort study, 2016-2021.

Aim: Children constitute an important and distinct subgroup of out-of-hospital cardiac arrest (OHCA) patients. This population-based cohort study aims to establish current age-specific population incidence, precipitating causes, circumstances, and outcome of paediatric OHCA, to guide a focused approach to prevention and intervention to improve outcomes. Methods: Data from the national Norwegian Cardiac Arrest Registry was extracted for the six-year period 2016-21 for persons aged <18 years. We present descriptive statistics for the population, resuscitation events, presumed causes, treatment, and outcomes, alongside age-specific incidence and total paediatric mortality rates. Results: Three hundred and eight children were included. The incidence of OHCA was 4.6 per 100 000 child-years and markedly higher in children <1 year at 20.9 child-years. Leading causes were choking, cardiac and respiratory disease, and sudden infant death syndrome. Overall, 21% survived to 30 days and 18% to one year. Conclusion: A registry-based approach enabled this study to delineate the characteristics and trajectories of OHCA events in a national cohort of children. Precipitating causes of paediatric OHCA are diverse compared to adults. Infants aged <1 year are at particularly high risk. Mortality is high, albeit lower than for adults in Norway. A rational community approach to prevention and treatment may focus on general infant care, immediate first aid by caretakers, and identification of vulnerable children by primary health providers. Cardiac arrest registries are a key source of knowledge essential for quality improvement and research into cardiac arrest in childhood.

Early detection of anastomotic leakage after pancreatoduodenectomy with microdialysis catheters: an observational Study.

BACKGROUND: Microdialysis catheters can detect focal inflammation and ischemia, and thereby have a potential for early detection of anastomotic leakages after pancreatoduodenectomy. The aim was to investigate whether microdialysis catheters placed near the pancreaticojejunostomy can detect leakage earlier than the current standard of care. METHODS: Thirty-five patients with a median age 69 years were included. Two microdialysis catheters were placed at the end of surgery; one at the pancreaticojejunostomy, and one at the hepaticojejunostomy. Concentrations of glucose, lactate, pyruvate, and glycerol were analyzed hourly in the microdialysate during the first 24 h, and every 2-4 h thereafter. RESULTS: Seven patients with postoperative pancreatic fistulae (POPF) had significantly higher glycerol levels (P < 0.01) in the microdialysate already in the first postoperative samples. Glycerol concentrations >400 µmol/L during the first 12 postoperative hours detected patients with POPF with a sensitivity of 100% and a specificity of 93% (P < 0.001). After 24 h, lactate and lactate-to-pyruvate ratio were significantly higher (P < 0.05) and glucose was significantly lower (P < 0.05) in patients with POPF. CONCLUSION: High levels of glycerol in microdialysate was an early detector of POPF. The subsequent inflammation was detected as increase in lactate and lactate-to-pyruvate ratio and a decrease in glucose (NCT03627559).

Circulatory Response to Rapid Volume Expansion and Cardiorespiratory Fitness in Fontan Circulation.

The role of dysfunction of the single ventricle in Fontan failure is incompletely understood. We aimed to evaluate hemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology. In 38 consecutive patients (median age = 16.6 years, 16 females), heart catheterization was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO2peak) and ventilatory threshold (VT). Median CVP increased from 13 mmHg at baseline to 14.5 mmHg (p < 0.001) at steady state. CVP increased by more than 20% in eight patients. Median VEDP increased from 10 mmHg at baseline to 11.5 mmHg (p < 0.001). Ten patients had elevated VEDP at steady state, and in 21, VEDP increased more than 20%. The transpulmonary pressure difference (CVP‒VEDP) and CVP were consistently higher in patients with right ventricular morphology across repeated measurements. CVP at any stage was associated with VO2peak and VT. VEDP after volume expansion was associated with VT. Preload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood.ClinicalTrials.gov identifier NCT02378857.

A man in his thirties with right ventricular heart failure, jaundice and abdominal pain. / En mann i 30-årene med høyresidig hjertesvikt, ikterus og magesmerter.

BACKGROUND: The combination of jaundice and acute abdominal pain is a common clinical problem associated with a broad array of aetiologies. CASE PRESENTATION: A 36-year-old male with Down's syndrome and Eisenmenger's syndrome presented with abdominal pain, jaundice and acute liver failure. Initial transabdominal ultrasound and subsequent magnetic resonance cholangiopancreatography (MRCP) revealed gallbladder stones, but no common bile duct stones. During the course of the patient's hospital admission, his liver chemistries were consistently elevated. Thus, endoscopic retrograde cholangiography (ERC) with sphincterotomy was performed, despite the anaesthesiological risk associated with his chronic heart failure. However, the ERC and sphincterotomy did not relieve the patient's symptoms and had no apparent effect on his abnormal liver chemistries. By the end of his hospital stay, the patient recovered spontaneously and was discharged with no final conclusion having been reached. An unexpected turn of events led us to conclude upon a diagnosis a few weeks later. INTERPRETATION: This case illustrates the challenges of a multidisciplinary approach in a complex patient, and an overlooked detail that became a lesson to learn from.

Elevated levels of the secreted wingless agonist R-spondin 3 in preeclamptic pregnancies.

OBJECTIVE: Preeclampsia is a syndrome characterized by hypertension and poor placental development. The developmental wingless (Wnt) pathway plays an important role in placental development and we hypothesized that Wnt signaling would be dysregulated in preeclampsia. METHODS: To elucidate aberrations in the Wnt signaling pathway we conducted a pathway analysis on placental mRNA in late-onset preeclampsia and normal pregnancy from the STORK study [n = 10 in each group, RNA sequencing (RNAseq)] to identify differentially expressed genes. In addition, we compared circulating levels of secreted Wnt agonists and antagonists at term pregnancy and 6 months postpartum from an acute preeclampsia study (preeclampsia n = 34, normal pregnancy n = 61). RESULTS: We found circulating and placental mRNA levels of the secreted Wnt agonist R-spondin 3 (RSPO3) at term elevated in preeclampsia. Increased plasma RSPO3 was associated with high mean arterial pressure. Further, pathway analysis of placental tissue revealed elevated mRNA levels of upstream ligands WNT6 and WNT10A and frizzled receptors 2 and 4 in preeclampsia and downstream activation of the noncanonical Ca/NFAT pathway. Finally, plasma dickkopf 3 was decreased in preeclampsia 6 months postpartum. CONCLUSION: We identify a potential role for RSPO3 and activation of noncanonical Wnt signaling in preeclampsia.

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock.

AIMS: Heart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction. METHODS AND RESULTS: The LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary intervention-treated ST-elevation myocardial infarction herein underwent a post hoc analysis. Blood samples were drawn from inclusion to Day 5 and at 42 day follow-up, and biomarkers were measured with enzyme immunoassays. Regional myocardial contractility was measured by echocardiography as wall motion score index (WMSI). The cardiogenic shock group (n = 9) was compared with the non-shock group (n = 52). Controls (n = 44) were age-matched and sex-matched healthy individuals. C4bc, C3bc, C3bBbP, and sC5b-9 were elevated in patients at inclusion compared with controls (P < 0.01). The shock group had higher levels compared with the non-shock group for all activation products except C3bBbP (P < 0.05). At Day 42, all products were higher in the shock group (P < 0.05). In the shock group, sC5b-9 correlated significantly with WMSI at baseline (r = 0.68; P = 0.045) and at Day 42 (r = 0.84; P = 0.036). Peak sC5b-9 level correlated strongly with WMSI at Day 42 (r = 0.98; P = 0.005). Circulating endothelial cell activation markers sICAM-1 and sVCAM-1 were higher in the shock group during the acute phase (P < 0.01), and their peak levels correlated with sC5b-9 peak level in the whole HF population (r = 0.32; P = 0.014 and r = 0.30; P = 0.022, respectively). CONCLUSIONS: Complement activation discriminated cardiogenic shock from non-shock in acute ST-elevation myocardial infarction complicated by HF and correlated with regional contractility and endothelial cell activation, suggesting a pathogenic role of complement in this condition.

Transpulmonary thermodilution (PiCCO) measurements in children without cardiopulmonary dysfunction: large interindividual variation and conflicting reference values.

BACKGROUND: The PiCCO system, based on transpulmonary thermodilution, is one of the few tools available for continuous hemodynamic monitoring in children. However, published data for some of the derived variables reveal indexed values that seem questionable. AIMS: The aim of this study was to collect data from hemodynamically normal children and compare these to existing reference values. Furthermore, we sought to explore if indexing some of the variables differently could improve the clinical application of the obtained values. METHODS: This is a prospective observational study in a tertiary university hospital including 31 children without cardiopulmonary disease scheduled for major neurosurgery. Measurements were performed after induction of general anesthesia. RESULTS: Median age was 8 months. PiCCO-derived median Cardiac Index (CI) was 3.8 l · min(-1) · m(-2) (range 2.6-6.6), reference range 3.0-5.0, median Global End-Diastolic Volume Index (GEDVI) was 366 ml · m(-2) (range 269-685), reference range 680-800, whereas median Extravascular Lung Water Index (EVLWI) was 12 ml · kg(-1) (range 7-31), reference range 3-7. All measured variables had a high interindividual variation, especially in children weighing less than 15 kg. CONCLUSIONS: Values obtained by the PiCCO system in children have a wide range, and should therefore be interpreted with caution. Current reference values published for GEDVI and EVLWI are not applicable in children; the former is too high and the latter too low, and should not guide clinical practice. Indexing by other physiological indices may reduce this problem. Using current variables, we find GEDVI 280-590 ml · m(-2) and ELWI 7-27 ml · kg(-1) to be typical ranges for children.

Elevated inflammatory markers in preeclamptic pregnancies, but no relation to systemic arterial stiffness.

OBJECTIVES: To investigate if circulating markers of systemic and vascular inflammation are associated with systemic arterial properties at term and 6months post-partum in women with preeclampsia (PE) and normal pregnancy (NP). STUDY DESIGN: Longitudinal, sampling at term and 6months post-partum in 34 women (32±6years) with PE and 61 women (32±5years) with NP. MAIN OUTCOME MEASURES: Circulating markers related to systemic and vascular inflammation were measured by enzyme immune-assay. Systemic arterial properties were estimated by Doppler (transthoracic echocardiography) and calibrated right subclavian artery pulse traces. RESULTS: CXCL16, soluble tumor necrosis factor receptor type 1 (sTNF-R1), monocyte chemoattractant peptide 1, pentraxin 3 and soluble vascular adhesion molecule 1 (sVCAM-1) were elevated at term in PE, and sTNF-R1 remained elevated 6months post partum compared to NP. However, apart from a negative correlation between mean arterial pressure and sTNF-R1 and sVCAM-1 at term, no associations between systemic and vascular inflammatory markers and systemic arterial properties as reflected by characteristic impedance and arterial elastance, representing proximal aortic stiffness and effective arterial elastance, were found at any time point. CONCLUSIONS: Preeclamptic pregnancies are characterized by increased circulating levels of systemic and vascular inflammatory markers. However, these are not associated with systemic arterial properties at term or 6months post partum.

Changes in blood pressure and cardiac output during cesarean delivery: the effects of oxytocin and carbetocin compared with placebo.

BACKGROUND: Little is known about maternal hemodynamics after Cesarean delivery. Uterine contractions may increase cardiac output. Oxytocin is the first-line treatment for uterine atony, although the effects of the long-acting oxytocin analogue carbetocin are comparable with that of oxytocin. The authors analyzed the effects of i.v. oxytocin 5 U, carbetocin 100 µg, and placebo on hemodynamics, uterine tone, adverse events, and blood loss after Cesarean delivery. METHODS: This was a randomized, double-blinded, placebo-controlled, parallel-group comparison of carbetocin and oxytocin after elective Cesarean delivery of singletons under spinal anesthesia (n = 76). Continuously measured invasive systolic arterial pressure was the primary outcome measure. RESULTS: The mean systolic arterial pressure decrease was 28 mmHg (95% CI, 22-34) after oxytocin and 26 mmHg (95% CI, 20-31) after carbetocin. The decrease was greatest after 80 (95% CI, 71-89) and 63 s (95% CI, 55-72), respectively (P = 0.006). The differences were nearly undetectable after 2.5 min, although the effect of carbetocin was slightly greater than placebo (P < 0.001). The group differences in systolic arterial pressure decreased over 5 min and were gone at 1 h. Heart rate and cardiac output increased in all three groups. Stroke volume increased after oxytocin and carbetocin but was unchanged after placebo. CONCLUSIONS: The hemodynamic side effects of oxytocin 5 U and carbetocin 100 µg were comparable. The lack of an increase in stroke volume in the placebo group challenges the theory that uterine contraction causes autotransfusion of uterine blood, leading to an increase in preload.

Increased arterial stiffness in pre-eclamptic pregnancy at term and early and late postpartum: a combined echocardiographic and tonometric study.

BACKGROUND: Pre-eclampsia (PE) is characterized by hypertension and proteinuria, and complicates from 3%-10% of all pregnancies. The hemodynamic pathophysiology of the heart and systemic arteries in pre-eclamptic patients has not been well described. We therefore performed a comprehensive comparison of the systemic arterial properties at term and at 6 months postpartum in women with PE and in women with normal pregnancy (NP) and in nonpregnant women with a previous pre-eclamptic pregnancy (PPEP). METHODS: The comparison included 40 patients with PE, 40 others with a PPEP (at 3.5±1.0 years postpartum), and 65 women who had had an NP. Noninvasive estimates of blood flow and pressure in the aortic root were made with echocardiography and calibrated right subclavian artery pulse traces obtained through tonometry. Total arterial compliance (C), arterial elastance (Ea), characteristic impedance (Z0), and peripheral arterial resistance (R) were estimated both through the use of a three-element Windkessel model and Fourier analysis of pressure and flow data. RESULTS: At term, Z0, Ea, and R were higher by 37%, 25%, and 23%, respectively (all P < 0.05) in women with PE than in those with an NP, and C was lower by 12% (P < 0.05). The values of Z0, Ea, and R remained elevated at 6 months postpartum in women who had had PE, and were also elevated in those with a PPEP, as compared to their values in NP. CONCLUSIONS: Our results demonstrate that pre-eclamptic pregnancies are characterized by a higher resistance throughout the arterial system. The altered arterial properties (Ea, Z0, and R) persisted at 6 months after PE and were also elevated at 3 years postpartum in women with a PPEP, indicating that PE induces long-standing cardiovascular disturbances.

Clinical experience with microdialysis catheters in pediatric liver transplants.

Ischemic vascular complications and rejection occur more frequently with pediatric liver transplants versus adult liver transplants. Using intrahepatic microdialysis catheters, we measured lactate, pyruvate, glucose, and glycerol values at the bedside for a median of 10 days in 20 pediatric liver grafts. Ischemia (n = 6), which was defined as a lactate level > 3.0 mM and a lactate/pyruvate ratio > 20, was detected without a measurable time delay with 100% sensitivity and 86% specificity. Rejection (n = 8), which was defined as a lactate level > 2.0 mM and a lactate/pyruvate ratio < 20 lasting for 6 or more hours, was detected with 88% sensitivity and 45% specificity. With additional clinical criteria, the specificity was 83% without a decrease in the sensitivity. Rejection was detected at a median of 4 days (range = 1-7 days) before alanine aminotransferase increased (n = 5, P = 0.11), at a median of 4 days (range = 2-9 days) before total bilirubin increased 25% or more (n = 7, P = 0.04), and at a median of 6 days (range = 4-11 days) before biopsy was performed (n = 8, P = 0.05). In conclusion, microdialysis catheters can be used to detect episodes of ischemia and rejection before current standard methods in pediatric liver transplants with clinically acceptable levels of sensitivity and specificity. The catheters were well tolerated by the children, and no major complications related to the catheters were observed.

Inflammatory markers sampled by microdialysis catheters distinguish rejection from ischemia in liver grafts.

Rejection and ischemia are serious complications after liver transplantation. Early detection is mandatory, but specific markers are largely missing, particularly for rejection. The objective of this study was to explore the ability of microdialysis catheters inserted in liver grafts to detect and discriminate rejection and ischemia through postoperative measurements of inflammatory mediators. Microdialysis catheters with a 100-kDa pore size were inserted into 73 transplants after reperfusion. After the study's completion, complement activation product 5a (C5a), C-X-C motif chemokine 8 (CXCL8), CXCL10, interleukin-1 (IL-1) receptor antagonist, IL-6, IL-10, and macrophage inflammatory protein 1ß were analyzed en bloc in all grafts with biopsy-confirmed rejection (n = 12), in grafts with vascular occlusion/ischemia (n = 4), and in reference grafts with a normal postoperative course of circulating transaminase and bilirubin levels (n = 17). The inflammatory mediators were elevated immediately after graft reperfusion and decreased toward low, stable values during the first 24 hours in nonischemic grafts. In grafts suffering from rejection, CXCL10 increased significantly (P = 0.008 versus the reference group and P = 0.002 versus the ischemia group) 2 to 5 days before increases in circulating alanine aminotransferase and bilirubin levels. The area under the receiver operating characteristic curve was 0.81. Grafts with ischemia displayed increased levels of C5a (P = 0.002 versus the reference group and P = 0.008 versus the rejection group). The area under the curve was 0.99. IL-6 and CXCL8 increased with both ischemia and rejection. In conclusion, CXCL10 and C5a were found to be selective markers for rejection and ischemia, respectively.

Early bedside detection of ischemia and rejection in liver transplants by microdialysis.

This study was performed to explore whether lactate, pyruvate, glucose, and glycerol levels sampled via microdialysis catheters in the transplanted liver could be used to detect ischemia and/or rejection. The metabolites were measured at the bedside every 1 to 2 hours after the operation for a median of 10 days. Twelve grafts with biopsy-proven rejection and 9 grafts with ischemia were compared to a reference group of 39 grafts with uneventful courses. The median lactate level was significantly higher in both the ischemia group [5.8 mM (interquartile range = 4.0-11.1 mM)] and the rejection group [2.1 mM (interquartile range = 1.9-2.4 mM)] versus the reference group [1.5 mM (interquartile range = 1.1-1.9 mM), P < 0.001 for both]. The median pyruvate level was significantly increased only in the rejection group [185 µM (interquartile range = 155-206 µM)] versus the reference group [124 µM (interquartile range = 102-150 µM), P < 0.001], whereas the median lactate/pyruvate ratio and the median glycerol level were increased only in the ischemia group [66.1 (interquartile range = 23.9-156.7) and 138 µM (interquartile range = 26-260 µM)] versus the reference group [11.8 (interquartile range = 10.6-13.6), P < 0.001, and 9 µM (interquartile range = 9-24 µM), P = 0.002]. Ischemia was detected with 100% sensitivity and greater than 90% specificity when a positive test was repeated after 1 hour. In 3 cases of hepatic artery thrombosis, ischemia was detected despite normal blood lactate levels. Consecutive pathological measurements for 6 hours were used to diagnose rejection with greater than 80% sensitivity and specificity at a median of 4 days before the activity of alanine aminotransferase, the concentration of bilirubin in serum, or both increased. In conclusion, bedside measurements of intrahepatic lactate and pyruvate levels were used to detect ischemia and rejection earlier than current standard methods could. Discrimination from an uneventful patient course was achieved. Consequently, intrahepatic graft monitoring with microdialysis may lead to the earlier initiation of graft-saving treatment.

Systemic arterial response and ventriculo-arterial interaction during normal pregnancy.

BACKGROUND: During normal pregnancy (NP), cardiac output (CO) increases, and blood pressure and systemic vascular resistance are reduced. We wanted to evaluate systemic arterial properties and interaction between the left ventricle (LV) and systemic arteries during NP. The role of systemic arteries and their interaction with LV-function in this hemodynamic response, lack description. METHODS: We used noninvasive methods to study 65 healthy women (32 ± 5 years) with NP repeatedly at gestational weeks 14-16, 22-24, 36, and 6 months postpartum (PP). Aortic root pressure and flow were obtained by calibrated right subclavian artery pulse traces and aortic annular Doppler flow recordings. Arterial properties were described by estimates of total arterial compliance (C), proximal aortic stiffness (characteristic impedance (Z(0))), arterial elastance (Ea), and peripheral arterial resistance (R). Ventriculo-arterial coupling (VAC) was characterized by the ratio between arterial (E(a)I) and LV (E(LV)I) elastance index. RESULTS: During NP, CO increased by 20% due to increased heart rate and stroke volume. Mean arterial pressure was reduced by 10% (P < 0.001) as compared to 6 months PP. R was reduced by 5% (P < 0.01), Z(0) trended lower and C higher. E(a)I decreased (P < 0.01) and E(LV)I was reduced to a higher extent resulting in 29% increase of E(a)I/E(LV)I during NP (P < 0.01). CONCLUSIONS: During NP there is an increase in CO, and decrease in blood pressure and R whereas central aortic properties are less altered. The increased VAC index (E(a)I/E(LV)I) during NP indicates a decrease in LV-function not fully compensated for by vascular adaptation.

Changes in blood pressure during healthy pregnancy: a longitudinal cohort study.

OBJECTIVE: To study longitudinally changes in blood pressure (BP) and heart rate (HR) during healthy pregnancies and to evaluate the influence of parity, pregestational overweight, and excessive weight gain. METHODS: A prospective longitudinal cohort study of 57 healthy white women with singleton pregnancies. BP and HR were measured repeatedly at gestational age 14-16 weeks, 22-24 weeks, 30-32 weeks, 36 weeks, and 6 months postpartum using both an oscillometric measurement device (Dinamap) and finger arterial pressure (Finometer PRO). RESULTS: SBP, DBP, and mean arterial pressure (MAP) reached a statistically significant trough at gestational age 22-24 weeks using both measurement devices. When compared with the nonpregnant measurement, SBP at gestational age 22-24 weeks was 6.2 mmHg [95% confidence interval (95% CI) 1.3-11.2] lower measured by Finometer and 7.2 mmHg (95% CI 4.2-10.1) lower measured by Dinamap. DBP and MAP were 8.9 mmHg (95% CI 4.6-13.2) and 9.8 mmHg (95% CI 5.3-14.2) lower measured by Finometer. Measured by Dinamap, DBP and MAP were 4.5 mmHg (95% CI 1.7-7.3) and 5.4 mmHg (95% CI 2.8-7.9) lower at gestational age 22-24 weeks when compared with the nonpregnant state. SBP was significantly higher in women with pregestational BMI at least 25 kg/m with both measurement devices (both P < 0.05). There were no differences in SBP, DBP, or MAP depending on parity or excessive weight gain. CONCLUSION: BP measured repeatedly by two different noninvasive devices during pregnancy and postpartum showed a statistically significant drop in mid-pregnancy, followed by a progressive increase until term.